Homeopathy 2023; 112(03): 160-169
DOI: 10.1055/s-0042-1755364
Original Research Article

Arsenicum album Induces Cell Cycle Arrest and Apoptosis, and Inhibits Epithelial–Mesenchymal Transition in Hormone-Dependent MCF7 Breast Cancer Cells

Nilanjana Basu
1   Amity Institute Molecular Medicine & Stem Cell Research, Amity University, Noida, Uttar Pradesh, India
Manoj Garg
1   Amity Institute Molecular Medicine & Stem Cell Research, Amity University, Noida, Uttar Pradesh, India
Chanderdeep Tandon
2   Amity University Punjab, Mohali, India
Bhudev Chandra Das
1   Amity Institute Molecular Medicine & Stem Cell Research, Amity University, Noida, Uttar Pradesh, India
1   Amity Institute Molecular Medicine & Stem Cell Research, Amity University, Noida, Uttar Pradesh, India
2   Amity University Punjab, Mohali, India
› Author Affiliations
Funding None.


Background Arsenic trioxide (As2O3) has been in therapeutic use since the 18th century for various types of cancers including skin and breast; however, it gained popularity following FDA approval for its use against acute promyelocytic leukemia. This present work was designed to evaluate the anti-cancer potential of a homeopathic potency of arsenic trioxide (Arsenicum album 6C) in hormone-dependent breast cancer.

Methods Breast cancer cells (MCF7) were treated with Arsenicum album (Ars 6C) to evaluate its anti-proliferative and apoptotic potential. We examined the effect of Ars 6C on the cell cycle, wound healing, reactive oxygen species (ROS) generation, and modulation of expression of key genes which are aberrant in cancer.

Results Treating breast cancer cells with Ars 6C halted the cell cycle at the sub-G0 and G2/M phases, which could be attributed to DNA damage induced by the generation of ROS. Apoptotic induction was associated with upregulation of Bax expression, with concurrent downregulation of the Bcl-2 gene. Ars 6C was also seen to reverse epithelial to mesenchymal transition and reduce the migration of breast cancer cells.

Conclusion The findings suggest that Ars has significant anti-proliferative and apoptotic potential against breast cancer cells. Further studies are required to elucidate the mechanism by which Ars exerts its effect in the in vivo setting.

Authors' Contributions

N.B. conceptualized the study, performed experimental investigation and formal analysis, and was a major contributor in writing the manuscript. M.G. performed formal analysis. C.T. performed formal analysis. B.C.D. performed formal analysis. S.T. conceptualized the study and designed its methods, supervised the work and edited the manuscript.

Publication History

Received: 05 April 2022

Accepted: 28 June 2022

Article published online:
28 November 2022

© 2022. Faculty of Homeopathy. This article is published by Thieme.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Miller Jr WH, Schipper HM, Lee JS, Singer J, Waxman S. Mechanisms of action of arsenic trioxide. Cancer Res 2002; 62: 3893-3903
  • 2 Antman KH. Introduction: the history of arsenic trioxide in cancer therapy. Oncologist 2001; 6: 1-2
  • 3 Waxman S, Anderson KC. History of the development of arsenic derivatives in cancer therapy. Oncologist 2001; 6: 3-10
  • 4 Chen GQ, Zhu J, Shi XG. et al. In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR α/PML proteins. Blood 1996; 88: 1052-1061
  • 5 Douer D, Hu W, Giralt S, Lill M, DiPersio J. Arsenic trioxide (trisenox) therapy for acute promyelocytic leukemia in the setting of hematopoietic stem cell transplantation. Oncologist 2003; 8: 132-140
  • 6 Das D, Chatterjee A, Samanta G. et al. Arsenic contamination in groundwater in six districts of West Bengal, India: the biggest arsenic calamity in the world. Analyst (Lond) 1994; 119: 168N-170N
  • 7 Smith AH, Marshall G, Yuan Y. et al. Rapid reduction in breast cancer mortality with inorganic arsenic in drinking water. EBioMedicine 2014; 1: 58-63
  • 8 Calabrese EJ. The emergence of the dose-response concept in biology and medicine. Int J Mol Sci 2016; 17: 2034-2047
  • 9 Hahnemann S. Organon of Medicine. Combined 5th and 6th ed. Dudgeon RE and Boericke W (Translators). Delhi: B. Jain Publishers (P) Ltd.; 2008: 67
  • 10 World Health Organization.. Breast cancer now most common form of cancer: WHO taking action. Accessed June 26, 2021 at: https://www.who.int/news/item/03-02-2021-breast-cancer-now-most-common-form-of-cancer-who-taking-action
  • 11 Dai X, Cheng H, Bai Z, Li J. Breast cancer cell line classification and its relevance with breast tumor subtyping. J Cancer 2017; 8: 3131-3141
  • 12 Sihto H, Lundin J, Lundin M. et al. Breast cancer biological subtypes and protein expression predict for the preferential distant metastasis sites: a nationwide cohort study. Breast Cancer Res 2011; 13: R87-R97
  • 13 Agrawal S. Late effects of cancer treatment in breast cancer survivors. South Asian J Cancer 2014; 3: 112-115
  • 14 Das D, Chatterjee A, Mandal BK, Samanta G, Chakraborti D, Chanda B. Arsenic in ground water in six districts of West Bengal, India: the biggest arsenic calamity in the world. Part 2. Arsenic concentration in drinking water, hair, nails, urine, skin-scale and liver tissue (biopsy) of the affected people. Analyst (Lond) 1995; 120: 917-924
  • 15 Boericke W, Boericke O. Pocket Manual of Homeopathic Materia Medica. Reprinted. Kandern, Germany: Narayana Publishers; 2013: 94-96
  • 16 Ive EC, Couchman IMS, Reddy L. Therapeutic effect of Arsenicum album on leukocytes. Int J Mol Sci 2012; 13: 3979-3987
  • 17 Kundu SN, Mitra K, Bukhsh ARK. Efficacy of a potentized homoeopathic drug (Arsenicum album-30) in reducing cytotoxic effects produced by arsenic trioxide in mice: III. Enzymatic changes and recovery of tissue damage in liver. Complement Ther Med 2000; 8: 76-81
  • 18 Banerjee P, Biswas SJ, Belon P, Khuda-Bukhsh AR. A potentized homeopathic drug, Arsenicum album 200, can ameliorate genotoxicity induced by repeated injections of arsenic trioxide in mice. J Vet Med A Physiol Pathol Clin Med 2007; 54: 370-376
  • 19 Wong RSY. Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res 2011; 30: 87
  • 20 Ranjan A, Ramachandran S, Gupta N. et al. Role of phytochemicals in cancer prevention. Int J Mol Sci 2019; 20: 4981-4997
  • 21 Mondal J, Panigrahi AK, Khuda-Bukhsh AR. Anticancer potential of Conium maculatum extract against cancer cells in vitro: Drug-DNA interaction and its ability to induce apoptosis through ROS generation. Pharmacogn Mag 2014; 10: S524-S533
  • 22 Samadder A, Das S, Das J, Paul A, Boujedaini N, Khuda-Bukhsh AR. The potentized homeopathic drug, Lycopodium clavatum (5C and 15C) has anti-cancer effect on Hela cells in vitro. J Acupunct Meridian Stud 2013; 6: 180-187
  • 23 Saha S, Bhattacharjee P, Guha D. et al. Sulphur alters NFκB-p300 cross-talk in favour of p53-p300 to induce apoptosis in non-small cell lung carcinoma. Int J Oncol 2015; 47: 573-582
  • 24 Saha S, Hossain DMS, Mukherjee S. et al. Calcarea carbonica induces apoptosis in cancer cells in p53-dependent manner via an immuno-modulatory circuit. BMC Complement Altern Med 2013; 13: 230-249
  • 25 Frenkel M, Mishra BM, Sen S. et al. Cytotoxic effects of ultra-diluted remedies on breast cancer cells. Int J Oncol 2010; 36: 395-403
  • 26 Mukherjee A, Boujedaini N, Khuda-Bukhsh AR. Homeopathic Thuja 30C ameliorates benzo(a)pyrene-induced DNA damage, stress and viability of perfused lung cells of mice in vitro. J Integr Med 2013; 11: 397-404
  • 27 Dhanasekaran DN, Reddy EP. JNK signaling in apoptosis. Oncogene 2008; 27: 6245-6251
  • 28 Doan P, Musa A, Candeias NR, Emmert-Streib F, Yli-Harja O, Kandhavelu M. Alkylaminophenol induces G1/S phase cell cycle arrest in glioblastoma cells through p53 and cyclin-dependent kinase signaling pathway. Front Pharmacol 2019; 10: 330-346
  • 29 Szymański P, Olszewska P, Mikiciuk-Olasik E. et al. Novel tetrahydroacridine and cyclopentaquinoline derivatives with fluorobenzoic acid moiety induce cell cycle arrest and apoptosis in lung cancer cells by activation of DNA damage signaling. Tumour Biol 2017; 39: 1010428317695011
  • 30 Lv YG, Yu F, Yao Q, Chen JH, Wang L. The role of survivin in diagnosis, prognosis and treatment of breast cancer. J Thorac Dis 2010; 2: 100-110
  • 31 Garg H, Suri P, Gupta JC, Talwar GP, Dubey S. Survivin: a unique target for tumor therapy. Cancer Cell Int 2016; 16: 49-63
  • 32 Mita AC, Mita MM, Nawrocki ST, Giles FJ. Survivin: key regulator of mitosis and apoptosis and novel target for cancer therapeutics. Clin Cancer Res 2008; 14: 5000-5005
  • 33 Jha K, Shukla M, Pandey M. Survivin expression and targeting in breast cancer. Surg Oncol 2012; 21: 125-131
  • 34 Feroz W, Sheikh AMA. Exploring the multiple roles of guardian of the genome: P53. Egypt J Med Hum Genet 2020; 21: 49
  • 35 Roszkowska KA, Gizinski S, Sady M, Gajewski Z, Olszewski MB. Gain-of-function mutations in p53 in cancer invasiveness and metastasis. Int J Mol Sci 2020; 21: 1334-1347
  • 36 Chio IIC, Tuveson DA. ROS in cancer: the burning question. Trends Mol Med 2017; 23: 411-429
  • 37 Adhikary A, Chakraborty S, Mazumdar M. et al. Inhibition of epithelial to mesenchymal transition by E-cadherin up-regulation via repression of slug transcription and inhibition of E-cadherin degradation: dual role of scaffold/matrix attachment region-binding protein 1 (SMAR1) in breast cancer cells. J Biol Chem 2014; 289: 25431-25444
  • 38 Loh CY, Chai JY, Tang TF. et al. The E-cadherin and N-cadherin switch in epithelial-to-mesenchymal transition: signaling, therapeutic implications, and challenges. Cells 2019; 8: 1118-1151
  • 39 Wang X, Chen S, Shen T. et al. Trichostatin A reverses epithelial-mesenchymal transition and attenuates invasion and migration in MCF-7 breast cancer cells. Exp Ther Med 2020; 19: 1687-1694